Clcc1, or Chloride Channel CLIC Like 1, is an ER-resident chloride channel. It is crucial for maintaining ER ion homeostasis, participating in pathways such as regulating [Cl-]ER, [K+]ER, and ER Ca2+ homeostasis. It also has roles in processes like neutral lipid flux, nuclear pore complex assembly, and is involved in the unfolded protein response pathway [1,2,4,5]. Genetic models, especially knockout models, are valuable for studying its functions.

Conditional knockout of Clcc1 in mice cell-autonomously causes motor neuron loss, ER stress, misfolded protein accumulation, and characteristic ALS-like pathologies in the spinal cord, indicating its role in ALS-like pathologies [1]. In mice, loss of Clcc1 leads to liver steatosis and defects in nuclear pore complex assembly, showing its importance in hepatic neutral lipid flux and nuclear envelope morphogenesis [2]. In herpesvirus-infected cells, loss of Clcc1 results in a defect in nuclear egress, highlighting its role in herpesvirus nuclear egress [3].

In conclusion, Clcc1 is essential for maintaining ER ion homeostasis, and its functions extend to lipid metabolism, nuclear envelope morphogenesis, and viral infection processes. The study of Clcc1 knockout mouse models has significantly contributed to understanding its role in ALS-like pathologies, hepatic functions, and herpesvirus-host interactions.